Azabicyclic compounds

Enantiopure 1-azabicyclic compounds of dilferent ring size have also been prepared using the described method [245]. 

The same type of cascade cyclization has been applied to the one-step synthesis of fused azabicyclic compounds with medium to large-membered rings (Scheme 10). ... 

Reddy, P. G., Baskaran, S. (2004) Epoxide-initiated cationic cyclization of azides a novel method for the stereoselective construction of 5-hydroxymethyl azabicyclic compounds and application in the stereo- and enan-tioselective total synthesis of (+)- and ( —) -indolizidine 167B and 209D. J Org Chem 69, 3093-3101. 

Synthesis of bridged azabicyclic compounds using radical translocation reaction followed by cyclization has been reported [95JCS(P1)1801]. Treatment of bromoamide 126 with... 

The versatility of this approach was further expanded when Meyers and Libano20,21 showed that, using chloronitriles, azabicyclic compounds (12, n = 2, 3, or 4) can be obtained in good yields after two additional steps. 

The extension of this synthesis to a wide variety of 1-azabicyclic compounds containing in some cases oxygen and sulfur atoms in the ring has been promised for future publications. 

Scheme 8.8 Synthesis of 1-azabicyclic compounds from hydroxyimino diesters.

Bastable, J.W., Hobson, J.D., and Ridell, W.D. 1972. Transannular cyclization of cyclo-olefinic A-chloro-amines. Synthesis of azabicyclic compounds. J Chem Soc Perkin Trans 1, 2205-2213. 

Radical translocation/cyclization reactions in syntheses of bridged azabicyclic compounds 03H(59)429. 

Olesen, P.H., Swedberg, M.D.B., Eskesen, K., Judge, M.E., Egebjerg, J., Tonder, J.E., Rasmussen, T., Sheardown, M.J., Rimvall, K., 1997. Identification of novel (isoxazole)methylene-l-azabicyclic compounds with high affinity for the central nicotinic cholinergic receptor. Bioorg. Med. Chem. Lett. 7, 1963-1968. 

A new process for synthesis of 3-aminomethyl-3,5,5-trimethylcyclohexylamine (IPDA) has been investigated. The reaction was performed in two steps. In the first step bis (3-cyano-3,5,5 trimethylcyclohexylidene) azine (IPNA) was synthesized from 3-cyano-3,5,5 trimethyl- 1 oxo cyclohexane (IPN) and hydrazine hydrate in solvent. The reaction yield was nearly quantitative. In the second step the azine (IPNA) was hydrogenated under mild conditions on a Raney nickel or cobalt catalyst in the presence of a small amount of ammonia. Isophorone diamine (IPDA) was obtained at high yields (90-95 %). But the main interest of a such process is to minimize the production of byproducts (aminoalcohol, azabicyclic compound, secondary amine) and to use less severe pressure conditions than those generally employed. 

The epoxide-initiated Schmidt reaction proceeds in a similar fashion to the mercury-promoted version. Treatment of epoxyazide 40 with a Lewis acid brings about cyclization to give the aminodiazonium intermediate 42, regioslective ring expansion results in the bicyclic iminium ion 43, and in situ reduction of 43 affords 5-hydroxymethyl azabicyclic compound 44. This alcohol has been converted to indolizidine alkaloids 167B and 209D. 

Intramolecular addition of aminyl radicals has been more extensively studied in order to obtain azabicyclic compounds. The first report (Scheme 122) was made in 1970 by Heusler, who devised an elegant synthesis of chloroazatwistanes (309) (two epimers in 80% yield) by irradiating the N-chloroamine (308) in trifluoroacetic acid. While he did not propose a mechanism, it appears that the origin of the product 309 is in accord with an... 

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